The overall goal of this program is to emphasize scientific paradigms focused on treatment of local / regional disease, with the ultimate objective of achieving long term control of such tumors, while maintaining normal tissue integrity. The paradigm is being approached two ways: 1) Therapeutic approaches to increase tumor response or reduce normal tissue damage, and 2) Development of diagnostic methods to predict outcome or guide therapeutic decisions before or during treatment. The fact that radiation therapy is used as part of therapy for nearly all forms of cancer means that the clinical collaborations are varied and multidisciplinary. Members cross many disciplines, including molecular biology and signal transduction, transgenic model development, physiology, angiogenesis, hyperthermia, engineering, drug carrier development, imaging, radiation biology and clinical trial development and conduct. This program is centered in a clinical department, which helps to focus efforts toward translational studies. The program has incorporated MR and CT/PET imaging capabilities into research activities with the acquisition of this hardware for research purposes. Several protocols now include opportunities for direct acquisition of tissues and / or plasma samples that can be used for correlative science investigations. Significant improvement has been made in the basic science component of the program, with successful recruitment of clinical faculty with interests in transgenic models of human cancer and in translational studies involving breast cancer radiotherapy. The program sponsors several venues for interaction, offered on a bi-weekly to yearly basis to facilitate collaborations within and with other programs. Since the last competing renewal, members of this program have published 424 peer reviewed papers; over 90% of which have been directly related to cancer. Nearly 50% of the publications have involved inter- or intra- programmatic collaborations. The patient census has grown by 35%, from 978 treatment starts in 2004 to well over 1300 in 2007. The percentage of patients enrolled on protocols has averaged just over 6%. Accrual of minorities and women has averaged 18% and 57%, respectively. Clinical trial and grants management infrastructure has been substantially improved, which is paying dividends with respect to easing initiation of new investigator initiated trials. The Program includes 24 members from 5 basic and clinical departments. Total funding for program members is $12,819,957, of Which $8,288,024 is from peer-reviewed sources. A cancer focus is illustrated by $4,758,760 or 57.4% of funding from the NCI, the American Cancer Society or the Department of Defense.